Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors

Timothy J. Hobday, Rui Qin, Diane Reidy-Lagunes, Malcolm J. Moore, Jonathan Strosberg, Andreas Kaubisch, Manisha Shah, Hedy Lee Kindler, Heinz Josef Lenz, Helen Chen, Charles Erlichman

Research output: Contribution to journalArticle

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Abstract

Purpose: There are few effective therapies for pancreatic neuroendocrine tumors (PNETs). Recent placebo-controlled phase III trials of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor (VEGF)/platelet-derived growth factor receptor inhibitor sunitinib have noted improved progression-free survival (PFS). Preclinical studies have suggested enhanced antitumor effects with combined mTOR and VEGF pathway-targeted therapy. We conducted a clinical trial to evaluate combination therapy against these targets in PNETs. Patients and Methods: We conducted a two-stage single-arm phase II trial of the mTOR inhibitor temsirolimus 25 mg intravenously (IV) once per week and the VEGF-A monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in patients with well or moderately differentiated PNETs and progressive disease by RECIST within 7 months of study entry. Coprimary end points were tumor response rate and 6-month PFS. Results: A total of 58 patients were enrolled, and 56 patients were eligible for response assessment. Confirmed response rate (RR) was 41% (23 of 56 patients). PFS at 6 months was 79% (44 of 56). Median PFS was 13.2 months (95% CI, 11.2 to 16.6). Median overall survival was 34 months (95% CI, 27.1 to not reached). For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%). Conclusion: The combination of temsirolimus and bevacizumab had substantial activity and reasonable tolerability in a multicenter phase II trial, with RR of 41%, well in excess of single targeted agents in patients with progressive PNETs. Six-month PFS was a notable 79% in a population of patients with disease progression by RECIST criteria within 7 months of study entry. On the basis of this trial, continued evaluation of combination mTOR and VEGF pathway inhibitors is warranted.

Original languageEnglish (US)
Pages (from-to)1551-1556
Number of pages6
JournalJournal of Clinical Oncology
Volume33
Issue number14
DOIs
StatePublished - May 10 2015

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Neuroendocrine Tumors
Disease-Free Survival
Sirolimus
Vascular Endothelial Growth Factor A
Platelet-Derived Growth Factor Receptors
Lymphopenia
Proxy
Therapeutics
temsirolimus
Bevacizumab
Hyperglycemia
Fatigue
Disease Progression
Monoclonal Antibodies
Placebos
Clinical Trials
Hypertension
Survival
Population
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hobday, T. J., Qin, R., Reidy-Lagunes, D., Moore, M. J., Strosberg, J., Kaubisch, A., ... Erlichman, C. (2015). Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors. Journal of Clinical Oncology, 33(14), 1551-1556. https://doi.org/10.1200/JCO.2014.56.2082

Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors. / Hobday, Timothy J.; Qin, Rui; Reidy-Lagunes, Diane; Moore, Malcolm J.; Strosberg, Jonathan; Kaubisch, Andreas; Shah, Manisha; Kindler, Hedy Lee; Lenz, Heinz Josef; Chen, Helen; Erlichman, Charles.

In: Journal of Clinical Oncology, Vol. 33, No. 14, 10.05.2015, p. 1551-1556.

Research output: Contribution to journalArticle

Hobday, TJ, Qin, R, Reidy-Lagunes, D, Moore, MJ, Strosberg, J, Kaubisch, A, Shah, M, Kindler, HL, Lenz, HJ, Chen, H & Erlichman, C 2015, 'Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors', Journal of Clinical Oncology, vol. 33, no. 14, pp. 1551-1556. https://doi.org/10.1200/JCO.2014.56.2082
Hobday, Timothy J. ; Qin, Rui ; Reidy-Lagunes, Diane ; Moore, Malcolm J. ; Strosberg, Jonathan ; Kaubisch, Andreas ; Shah, Manisha ; Kindler, Hedy Lee ; Lenz, Heinz Josef ; Chen, Helen ; Erlichman, Charles. / Multicenter phase II trial of temsirolimus and bevacizumab in pancreatic neuroendocrine tumors. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 14. pp. 1551-1556.
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AU - Strosberg, Jonathan

AU - Kaubisch, Andreas

AU - Shah, Manisha

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